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Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.
ERIVEDGE capsule was administered as monotherapy at doses ≥ 150 mg orally daily in four open-label, uncontrolled, dose-ranging or fixed single dose clinical trials enrolling a total of 138 patients with advanced basal cell carcinoma (BCC). The median age of these patients was 61 years (range 21 to 101), 100% were White (including Hispanics), and 64% were male. The median duration of treatment was approximately 10 months (305 days; range 0.7 to 36 months); 111 patients received ERIVEDGE for 6 months or longer.
The most common adverse reactions ( ≥ 10%) were muscle spasms, alopecia, dysgeusia, weight loss, fatigue, nausea, diarrhea, decreased appetite, constipation, arthralgias, vomiting, and ageusia (Table 1).
Table 1: Adverse Reactions Occurring in ≥ 10% of Advanced BCC Patients
|MedDRA Preferred Term2||All aBCC1 Patients (N = 138)|
|All Grades3 (%)||Grade 3 (%)||Grade 4 (%)|
|Nausea||42 (30.4%)||1 (0.7%)||-|
|Diarrhea||40 (29.0%)||1 (0.7%)||-|
|General disorders and administration site conditions|
|Fatigue||55 (39.9%)||7 (5.1%)||1 (0.7%)|
|Weight loss||62 (44.9%)||10 (7.2%)||-|
|Metabolism and nutrition disorders|
|Decreased appetite||35 (25.4%)||3 (2.2%)||-|
|Musculoskeletal and connective tissue disorders|
|Muscle spasms||99 (71.7%)||5 (3.6%)||-|
|Arthralgias||22 (15.9%)||1 (0.7%)|
|Nervous system disorders|
|Skin and subcutaneous tissue disorders|
|1aBCC = Advanced Basal Cell Carcinoma.
2MedDRA = Medical Dictionary for Regulatory Activities.
3Grading according to NCI-CTCAE v3.0.
Read the Erivedge (vismodegib) Side Effects Center for a complete guide to possible side effects
Effects of Other Drugs on Vismodegib
Drugs that Inhibit or Induce Drug Metabolizing Enzymes
Vismodegib elimination involves multiple pathways. Vismodegib is predominantly excreted as an unchanged drug. Several minor metabolites are produced by multiple CYP enzymes. Although vismodegib is a substrate of CYP2C9 and CYP3A4 in vitro, CYP inhibition is not predicted to alter vismodegib systemic exposure since similar steady-state plasma vismodegib concentrations were observed in patients in clinical trials concomitantly treated with CYP3A4 inducers (i.e., carbamazepine, modafinil, phenobarbital) and those concomitantly treated with CYP3A4 inhibitors (i.e., erythromycin, fluconazole).
Drugs that Inhibit Drug Transport Systems
In vitro studies indicate that vismodegib is a substrate of the efflux transporter P-glycoprotein (P-gp). When ERIVEDGE is coadministered with drugs that inhibit P-gp (e.g. clarithromycin, erythromycin, azithromycin), systemic exposure of vismodegib and incidence of adverse events of ERIVEDGE may be increased.
Drugs that Affect Gastric pH
Drugs that alter the pH of the upper GI tract (e.g. proton pump inhibitors, H2-receptor antagonists, and antacids) may alter the solubility of vismodegib and reduce its bioavailability. However, no formal clinical study has been conducted to evaluate the effect of gastric pH altering agents on the systemic exposure of vismodegib. Increasing the dose of ERIVEDGE when coadministered with such agents is not likely to compensate for the loss of exposure. When ERIVEDGE is coadministered with a proton pump inhibitor, H2-receptor antagonist or antacid, systemic exposure of vismodegib may be decreased and the effect on efficacy of ERIVEDGE is unknown.
Effects of Vismodegib on Other Drugs
Results of a drug-drug interaction study conducted in cancer patients demonstrated that the systemic exposure of rosiglitazone (a CYP2C8 substrate) or oral contraceptives (ethinyl estradiol and norethindrone) is not altered when either drug is co-administered with vismodegib.
In vitro studies indicate that vismodegib is an inhibitor of CYP2C8, CYP2C9, CYP2C19 and the transporter BCRP. Vismodegib does not induce CYP1A2, CYP2B6, or CYP3A4/5 in human hepatocytes.
Read the Erivedge Drug Interactions Center for a complete guide to possible interactions
Last reviewed on RxList: 2/2/2012
Additional Erivedge Information
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